Practical issues concerning tear protein assays in dry eye

D’Souza, Sharon; Tong, Louis

doi:10.1186/s40662-014-0006-y

Cited by 37 publications

(48 citation statements)

References 122 publications

(165 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is possible that this phenomenon is due to the nature of most non-SS DE patients recruited at the Roski Eye Institute corneal clinic, a tertiary care clinic, who may represent a different spectrum of dry eye disease than populations in previous studies. Alternatively, differences in tear collection techniques, the use of glass capillaries versus elution from Schirmer’s strips or even the choice of an anesthetised versus an unanesthetised Schirmer’s test may also play a role 48 . It is important to note that analysis techniques have varied across studies from radial immunodiffusion to ELISA-based assays.…”

Section: Discussionmentioning

confidence: 99%

Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren’s Syndrome patients

Edman

Janga

Meng

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Cathepsin S (CTSS) activity is elevated in Sjögren’s Syndrome (SS) patient tears. Here we tested whether protease inhibition and cystatin C (Cys C) levels are reduced in SS tears, which could lead to enhanced CTSS-driven degradation of tear proteins. CTSS activity against Cys C, LF and sIgA was tested in SS or healthy control tears. Tears from 156 female subjects (33, SS; 33, rheumatoid arthritis; 31, other autoimmune diseases; 35, non-autoimmune dry eye (DE); 24, healthy controls) were analyzed for CTSS activity and Cys C, LF, and sIgA levels. Cys C and LF showed enhanced degradation in SS tears supplemented with recombinant CTSS, but not supplemented healthy control tears. CTSS activity was significantly increased, while Cys C, LF and sIgA levels were significantly decreased, in SS tears compared to other groups. While tear CTSS activity remained the strongest discriminator of SS in autoimmune populations, combining LF and CTSS improved discrimination of SS beyond CTSS in DE patients. Reductions in Cys C and other endogenous proteases may enhance CTSS activity in SS tears. Tear CTSS activity is reconfirmed as a putative biomarker of SS in an independent patient cohort while combined LF and CTSS measurements may distinguish SS from DE patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren’s Syndrome patients

Edman

Janga

Meng

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Many of these studies have shown differences in several tear molecules in DED patients compared to healthy subjects, or among the different types of DED. A number of reviews on the use of tears as a source of biomarkers have been published to date, including for non-ocular diseases [ 23 – 25 ] and in reviews specifically dedicated to DED [ 26 – 29 ].…”

Section: Tear Fluid Analysis In Ocular Diseasementioning

confidence: 99%

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

2016

View full text Add to dashboard Cite

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual.This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown.

show abstract

“…Significantly increased expression of IL-1α, IL-6, IL-8, TNF-α, and TGF-β1 was found in conjunctiva epithelium of SS patients when compared to healthy controls [ 15 ]. Other studies demonstrate that IL-1, IL-6, IL-8, TNF-α, interferon-γ (IFN-γ) and IL-17 are highly expressed in SS patient tears relative to non-SS patients [ 16 , 17 , 18 , 19 ], suggesting that elevated pro-inflammatory cytokines may be related to disease progression in SS patients. In this study, we specifically hypothesized that tear CTSS may directly increase pro-inflammatory cytokine expression in human corneal epithelial cells, an effect that may contribute to ocular surface inflammation in SS.…”

Section: Introductionmentioning

confidence: 99%

Cathepsin S Alters the Expression of Pro-Inflammatory Cytokines and MMP-9, Partially through Protease—Activated Receptor-2, in Human Corneal Epithelial Cells

Klinngam

Janga

et al. 2018

IJMS

View full text Add to dashboard Cite

Cathepsin S (CTSS) activity is increased in tears of Sjögren’s syndrome (SS) patients. This elevated CTSS may contribute to ocular surface inflammation. Human corneal epithelial cells (HCE-T cells) were treated with recombinant human CTSS at activity comparable to that in SS patient tears for 2, 4, 8, and 24 h. Acute CTSS significantly increased HCE-T cell gene and protein expression of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) from 2 to 4 h, while matrix metalloproteinase 9 (MMP-9), CTSS, and protease-activated receptor-2 (PAR-2) were increased by chronic CTSS (24 h). To investigate whether the increased pro-inflammatory cytokines and proteases were induced by CTSS activation of PAR-2, HCE-T cells were transfected with PAR-2 siRNA, reducing cellular PAR-2 by 45%. Cells with reduced PAR-2 expression showed significantly reduced release of IL-6, TNF-α, IL-1β, and MMP-9 into culture medium in response to acute CTSS, while IL-6, TNF-α, and MMP-9 were reduced in culture medium, and IL-6 and MMP-9 in cell lysates, after chronic CTSS. Moreover, cells with reduced PAR-2 expression showed reduced ability of chronic CTSS to induce gene expression of pro-inflammatory cytokines and proteases. CTSS activation of PAR-2 may represent a potential therapeutic target for amelioration of ocular surface inflammation in SS patients.

show abstract

Practical issues concerning tear protein assays in dry eye

Cited by 37 publications

References 122 publications

Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren’s Syndrome patients

Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren’s Syndrome patients

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

Cathepsin S Alters the Expression of Pro-Inflammatory Cytokines and MMP-9, Partially through Protease—Activated Receptor-2, in Human Corneal Epithelial Cells

Contact Info

Product

Resources

About